Hematopoietic stem cell transplantation (HSCT) which consists of the infusion of hematopoietic stem cells can cure a wide variety of diseases, including leukemia, lymphoma, myeloproliferative disorders, myelodysplastic syndrome (MDS), bone marrow (BM) failure syndromes, congenital immunodeficiencies, enzyme deficiencies and hemoglobinopathies.
Despite considerable progress in the management of the complications of HSCT, infection (additionally to regimen-related toxicity (RRT) and graft-versus-host-disease (GVHD) remains an important cause of post-transplant morbidity and mortality, mainly after allogeneic HSCT. The major advances in the management of infectious complications have come from better understanding of the mechanisms of the complex depression of immunity observed during the first months after transplant and their role in the predisposition to given infections, and also from well-designed therapeutic trials. Although the proportion of infectious deaths after allogeneic HSCT has decreased over the last two decades, much remains to be done to further decrease this risk and implement more efficient preventive and prophylactic strategies adapted to this high-risk population.
Moreover, even though the risk of infectious deaths is much lower after autologous transplant, the risks of the procedure are greater than those of conventional chemotherapy, and preventive policies should be implemented in any transplant program.
The spectrum of pathogens to which HSCT recipients are most susceptible follows a time line corresponding to the predominant immune defects. In the first month of HSCT, neutropenia is the principal host defense defect, predisposing patients to bacterial, fungal, and viral infections. After HSCT, qualitative dysfunction of phagocytes persists because of corticosteroids and other immunosuppressive agents. The risk of infection by opportunistic viruses, bacteria and filamentous fungi during this period is strongly associated with the severity of GVHD and the requirement for potent immunosuppressive regimens.
New approaches have thus been developed to minimize the likelihood of infections. For instance, granulocyte colony-stimulating factor [G-CSF or filgastrim] or granulocyte-macrophage colony-stimulating factor [GM-CSF or sargramostim] have been used since they shorten the duration of neutropenia after HSCT; however, no data were found that indicate whether these growth factors effectively reduce the attack rate of opportunistic diseases (including bacterial infections or fungal infections) and thus reduce mortality.
Therefore, the routine use of these growth factors after HSCT is controversial and no recommendation for their use can be made. It results that means useful for effectively preventing infections among hematopoietic stem cell transplantation (HSCT) recipients are still highly needed in order to improve their survival after HSCT.
Moreover, under stress conditions such as infection or inflammation the body rapidly needs to generate new blood cells that are adapted to the challenge. Haematopoietic cytokines are known to affect survival, expansion and differentiation of lineage committed progenitors1,2 but it has been debated whether long term haematopoietic stem cells (HSC) are susceptible to direct lineage-specifying effects of cytokines to produce a specific type of progenitors. Although genetic changes in transcription factor balance can sensitize HSC to cytokine instruction3, the initiation of HSC commitment is generally thought to be triggered by stochastic fluctuation in cell intrinsic regulators such as lineage specific transcription factors4,5,6,7, leaving cytokines to ensure survival and proliferation of the progeny cells at later differentiation stages8,9.